Bicyclol Attenuates Liver Inflammation Induced by Infection of Hepatitis C Virus via Repressing ROS-Mediated Activation of MAPK/NF-κB Signaling Pathway
Treatment with direct-acting antivirals (DAAs) cures most patients infected with hepatitis C virus (HCV) in the real world. However, some patients, especially those with the underlying advanced liver disease, have a limited reduction of liver injury after achieving a sustained viral response (SVR)....
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-12-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.01438/full |
| _version_ | 1819260128610746368 |
|---|---|
| author | Hu Li Jian-Rui Li Meng-Hao Huang Jin-Hua Chen Xiao-Qin Lv Li-Li Zou Jia-Li Tan Biao Dong Zong-Gen Peng Zong-Gen Peng Jian-Dong Jiang Jian-Dong Jiang Jian-Dong Jiang |
| author_facet | Hu Li Jian-Rui Li Meng-Hao Huang Jin-Hua Chen Xiao-Qin Lv Li-Li Zou Jia-Li Tan Biao Dong Zong-Gen Peng Zong-Gen Peng Jian-Dong Jiang Jian-Dong Jiang Jian-Dong Jiang |
| author_sort | Hu Li |
| collection | DOAJ |
| description | Treatment with direct-acting antivirals (DAAs) cures most patients infected with hepatitis C virus (HCV) in the real world. However, some patients, especially those with the underlying advanced liver disease, have a limited reduction of liver injury after achieving a sustained viral response (SVR). Bicyclol was widely used in clinics for the treatment of a variety of liver injuries but with an unknown mechanism for the treatment of hepatitis C. We investigated the anti-inflammatory effects and mechanisms of bicyclol in HCV-infected hepatocytes and further confirmed the putative results in a mouse hepatitis model induced by the coinjection of polyinosinic-polycytidylic acid [poly (I:C)] and D-galactosamine (D-GalN). The results showed that the activation of nuclear factor kappa B (NF-κB) and the subsequent increase of inflammatory factors were directly induced by HCV infection and were persistent after clearance of the virus in Huh7.5 cells. Bicyclol decreased the activation of NF-κB and the levels of inflammatory factors in HCV-infected hepatocytes by inhibiting the activation of the ROS-MAPK-NF-κB pathway, and the effect was synergistic with DAAs in HCV-infected hepatocytes. Bicyclol attenuated the ROS-MAPK-NF-κB axis via recovering mitochondrial function without a dependence on dihydronicotinamide adenine dinucleotide phosphate oxidase and superoxide dismutases. The anti-inflammatory effects and mechanism of bicyclol were verified in mouse hepatitis induced by the coinjection of poly(I:C)/D-GalN. Bicyclol directly ameliorates the chronic inflammation caused by HCV infection and might be used with DAAs or after DAA therapy for ultimately curing chronic hepatitis C. |
| first_indexed | 2024-12-23T19:20:59Z |
| format | Article |
| id | doaj.art-b94f0029016a49858255646f895beb5a |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-23T19:20:59Z |
| publishDate | 2018-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-b94f0029016a49858255646f895beb5a2022-12-21T17:34:10ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-12-01910.3389/fphar.2018.01438418956Bicyclol Attenuates Liver Inflammation Induced by Infection of Hepatitis C Virus via Repressing ROS-Mediated Activation of MAPK/NF-κB Signaling PathwayHu Li0Jian-Rui Li1Meng-Hao Huang2Jin-Hua Chen3Xiao-Qin Lv4Li-Li Zou5Jia-Li Tan6Biao Dong7Zong-Gen Peng8Zong-Gen Peng9Jian-Dong Jiang10Jian-Dong Jiang11Jian-Dong Jiang12Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaKey Laboratory of Biotechnology of Antibiotics, The National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaKey Laboratory of Biotechnology of Antibiotics, The National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaTreatment with direct-acting antivirals (DAAs) cures most patients infected with hepatitis C virus (HCV) in the real world. However, some patients, especially those with the underlying advanced liver disease, have a limited reduction of liver injury after achieving a sustained viral response (SVR). Bicyclol was widely used in clinics for the treatment of a variety of liver injuries but with an unknown mechanism for the treatment of hepatitis C. We investigated the anti-inflammatory effects and mechanisms of bicyclol in HCV-infected hepatocytes and further confirmed the putative results in a mouse hepatitis model induced by the coinjection of polyinosinic-polycytidylic acid [poly (I:C)] and D-galactosamine (D-GalN). The results showed that the activation of nuclear factor kappa B (NF-κB) and the subsequent increase of inflammatory factors were directly induced by HCV infection and were persistent after clearance of the virus in Huh7.5 cells. Bicyclol decreased the activation of NF-κB and the levels of inflammatory factors in HCV-infected hepatocytes by inhibiting the activation of the ROS-MAPK-NF-κB pathway, and the effect was synergistic with DAAs in HCV-infected hepatocytes. Bicyclol attenuated the ROS-MAPK-NF-κB axis via recovering mitochondrial function without a dependence on dihydronicotinamide adenine dinucleotide phosphate oxidase and superoxide dismutases. The anti-inflammatory effects and mechanism of bicyclol were verified in mouse hepatitis induced by the coinjection of poly(I:C)/D-GalN. Bicyclol directly ameliorates the chronic inflammation caused by HCV infection and might be used with DAAs or after DAA therapy for ultimately curing chronic hepatitis C.https://www.frontiersin.org/article/10.3389/fphar.2018.01438/fullbicyclolhepatitis C virusanti-inflammatory therapyinflammatory factoroxidative stress |
| spellingShingle | Hu Li Jian-Rui Li Meng-Hao Huang Jin-Hua Chen Xiao-Qin Lv Li-Li Zou Jia-Li Tan Biao Dong Zong-Gen Peng Zong-Gen Peng Jian-Dong Jiang Jian-Dong Jiang Jian-Dong Jiang Bicyclol Attenuates Liver Inflammation Induced by Infection of Hepatitis C Virus via Repressing ROS-Mediated Activation of MAPK/NF-κB Signaling Pathway Frontiers in Pharmacology bicyclol hepatitis C virus anti-inflammatory therapy inflammatory factor oxidative stress |
| title | Bicyclol Attenuates Liver Inflammation Induced by Infection of Hepatitis C Virus via Repressing ROS-Mediated Activation of MAPK/NF-κB Signaling Pathway |
| title_full | Bicyclol Attenuates Liver Inflammation Induced by Infection of Hepatitis C Virus via Repressing ROS-Mediated Activation of MAPK/NF-κB Signaling Pathway |
| title_fullStr | Bicyclol Attenuates Liver Inflammation Induced by Infection of Hepatitis C Virus via Repressing ROS-Mediated Activation of MAPK/NF-κB Signaling Pathway |
| title_full_unstemmed | Bicyclol Attenuates Liver Inflammation Induced by Infection of Hepatitis C Virus via Repressing ROS-Mediated Activation of MAPK/NF-κB Signaling Pathway |
| title_short | Bicyclol Attenuates Liver Inflammation Induced by Infection of Hepatitis C Virus via Repressing ROS-Mediated Activation of MAPK/NF-κB Signaling Pathway |
| title_sort | bicyclol attenuates liver inflammation induced by infection of hepatitis c virus via repressing ros mediated activation of mapk nf κb signaling pathway |
| topic | bicyclol hepatitis C virus anti-inflammatory therapy inflammatory factor oxidative stress |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.01438/full |
| work_keys_str_mv | AT huli bicyclolattenuatesliverinflammationinducedbyinfectionofhepatitiscvirusviarepressingrosmediatedactivationofmapknfkbsignalingpathway AT jianruili bicyclolattenuatesliverinflammationinducedbyinfectionofhepatitiscvirusviarepressingrosmediatedactivationofmapknfkbsignalingpathway AT menghaohuang bicyclolattenuatesliverinflammationinducedbyinfectionofhepatitiscvirusviarepressingrosmediatedactivationofmapknfkbsignalingpathway AT jinhuachen bicyclolattenuatesliverinflammationinducedbyinfectionofhepatitiscvirusviarepressingrosmediatedactivationofmapknfkbsignalingpathway AT xiaoqinlv bicyclolattenuatesliverinflammationinducedbyinfectionofhepatitiscvirusviarepressingrosmediatedactivationofmapknfkbsignalingpathway AT lilizou bicyclolattenuatesliverinflammationinducedbyinfectionofhepatitiscvirusviarepressingrosmediatedactivationofmapknfkbsignalingpathway AT jialitan bicyclolattenuatesliverinflammationinducedbyinfectionofhepatitiscvirusviarepressingrosmediatedactivationofmapknfkbsignalingpathway AT biaodong bicyclolattenuatesliverinflammationinducedbyinfectionofhepatitiscvirusviarepressingrosmediatedactivationofmapknfkbsignalingpathway AT zonggenpeng bicyclolattenuatesliverinflammationinducedbyinfectionofhepatitiscvirusviarepressingrosmediatedactivationofmapknfkbsignalingpathway AT zonggenpeng bicyclolattenuatesliverinflammationinducedbyinfectionofhepatitiscvirusviarepressingrosmediatedactivationofmapknfkbsignalingpathway AT jiandongjiang bicyclolattenuatesliverinflammationinducedbyinfectionofhepatitiscvirusviarepressingrosmediatedactivationofmapknfkbsignalingpathway AT jiandongjiang bicyclolattenuatesliverinflammationinducedbyinfectionofhepatitiscvirusviarepressingrosmediatedactivationofmapknfkbsignalingpathway AT jiandongjiang bicyclolattenuatesliverinflammationinducedbyinfectionofhepatitiscvirusviarepressingrosmediatedactivationofmapknfkbsignalingpathway |